Tumbleweeds is set in and around the town of Grimy Gulch, whose population was stated as 49 (later it was marked out and incremented to 50, and sometimes is revised down when the villain Snake-Eye leaves town), in an unspecified Western territory. Other locations include the nearby village of the Poohawk tribe of Native Americans, and the US Army outpost Fort Ridiculous, manned by the 6 7/8 Cavalry.

Tumbleweeds, the main character, is a laconic cowpoke who would rather be anywhere else, but has no real ambition to do anything. Like his namesake, he is content to tumble wherever human foibles may carry him. His worst nightmare is to be caught by, and married to, Hildegard Hamhocker.
Blossom, Tumbleweed's first horse; usually found asleep.